The effect of birth weight on clottable and intact fibrinogen levels: a twin study

Several studies in singletons have found an association between low birth weight and increased plasma concentrations of clotting factors in adult life. Twins provide an opportunity to assess the possible contribution of genetic factors to this association. Forty-four monozygotic and 60 dizygotic same-sex twin pairs aged 19-50 years and 78 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from an obstetric database. Associations between both adult clottable fibrinogen (measured by the Clauss method) and intact fibrinogen (measured by the immunoprecipitation test), and birth weight were assessed by linear regression with adjustment for current age, gender, smoking and body mass index. Twins were significantly lighter at birth than singleton controls, but did not differ significantly in adult height, weight or fibrinogen levels from the singleton controls. There was a significant inverse association between birth weight and clottable fibrinogen levels among singleton controls [-0.22 g L-1 kg(-1) (95% CI: -0.41,-0.03), P = 0.03], but not in unpaired twins. For intact fibrinogen there was no significant association with birth weight in either singleton controls or twins. In the within-pair analysis in twins there was a significant inverse association between differences in birth weight and clottable fibrinogen levels in dizygotic twin pairs [-0.34 g L-1 kg(-1) (95% CI: -0.65,-0.02), P = 0.04], but not in monozygotic twin pairs [-0.12 g L-1 kg(-1) (95% CI: -0.53, 0.28), P = 0.54]. These results support the possibility that genetic factors may contribute to the association between low birth weight and clottable fibrinogen levels.